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The low levels of nerve growth factor and its upstream regulatory kinases in prion infection is reversed by resveratrol.

Abstract：

:Resveratrol shows ability to eliminate prion replication, but the exact mechanism for prion eradication was not clear yet. Our previous studies demonstrate a downregulation of brain-derived nerve growth factor (BDNF) during prion infection, meanwhile recovery of cerebral nerve growth factor (NGF) level by resveratrol treatment has been reported in other neurodegenerative models. To obtain the possible changes of brain NGF and its upstream regulatory cascade during prion infection and after removal of prion propagation, the levels of NGF and its upstream regulatory factors in various prion-infected and prion-eradicated SMB cell lines and mice brains inoculated with various SMB cellular lysates were assessed with various methodologies. The levels of NGF were significantly decreased during prion replication, while recovered after removal of PrPSc by resveratrol in vitro. Morphological assays revealed that the NGF signals mainly colocalized within neurons, but not in the proliferative astrocytes and microglia. The upstream positive regulatory kinases, such as p-CREB, p-CaMKIV, CaMKK2 were decreased in the prion infected cells and mice brains, whereas the negative regulatory one, p-CaMKK2, was increased. The aberrant situations of those kinases in prion infected cell lines or mice brains could be also partially reversed by removal of prion agent. Moreover, we demonstrated that the signals of CaMKK2 and p-CaMKK2 were also distributed predominately in neurons in the brain tissues. The data illustrate a direct linkage of abnormally repressive NGF and its upstream regulatory kinases with prion infection. Resveratrol has not only the ability to inhibit prion replication, but also to improve the expression of NGF via CaMKK2/CaMKIV cascade, which might benefit the microenvironment in brains.

journal_name

Neurosci Res

journal_title

Neuroscience research

authors

Hu C,Chen C,Chen J,Xiao K,Wang J,Shi Q,Ma Y,Gao LP,Wu YZ,Liu L,Xia Y,Yan P,Maimaitiming A,Zhou DH,Zhang LN,Chen ZB,Dong XP

doi

10.1016/j.neures.2019.12.019

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

52-62

eissn

0168-0102

issn

1872-8111

pii

S0168-0102(19)30555-3

journal_volume

162

pub_type

杂志文章

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The low levels of nerve growth factor and its upstream regulatory kinases in prion infection is reversed by resveratrol.